Wide-field retinal imaging system

ABSTRACT

A retinal imager for imaging a retina of an eye includes an illumination source operable to generate illumination light and a beam splitter operable to receive the illumination light and direct the illumination light along an optical axis. The retinal imager also includes a field lens disposed along the optical axis and an objective lens disposed along the optical axis and operable to contact a cornea of the eye. An aerial image is formed adjacent to the field lens. The retinal imager further includes an image sensor and one or more lenses disposed along the optical axis between the beam splitter and the image sensor. The one or more lenses are operable to form a sensor image at the image sensor.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/228,669, filed on Aug. 4, 2016, entitled “Wide-Field Retinal ImagingSystem with Optical Coherence Tomography,” which claims priority to U.S.Provisional Patent Application No. 62/201,243, filed on Aug. 5, 2015,entitled “Wide-Field Retinal Imaging System with Optical CoherenceTomography,” the disclosures of both of which are hereby incorporated byreference in their entirety for all purposes.

BACKGROUND OF THE INVENTION

Retinal imaging relates to systems that capture a digital image of theretina, blood vessels, and optic nerve located at the back of the eye.These images can be used for the early detection and management ofdiseases of the eyes.

Although retinal imaging systems have been developed, there is a need inthe art for improved methods and systems related to retinal imaging.

SUMMARY OF THE INVENTION

The present invention relates generally to methods and systems foroptical devices. More particularly, embodiments of the present inventionprovide methods and systems related to retinal imaging with opticalcoherence tomography (OCT).

Embodiments of the present invention address issues related tosensitivity to scattering from the eye lens and cornea and provide asystem characterized by small size, weight, and an appropriate physicalconfiguration. Embodiments are characterized by no visible focused ghostimages, low ghost background, and high resolution while achieving awide-field imaging and field of regard to at least the equator. Asdescribed herein, embodiments provide uniform illumination and efficientuse of illumination light, are able to be sanitized and have a formfactor that enables insertion into small eye sockets. Additionally,embodiments enable the addition of image guided OCT while employing adesign that avoids scattering and glare. These and other embodiments ofthe invention along with many of its advantages and features aredescribed in more detail in conjunction with the text below and attachedfigures.

Embodiments of the present invention achieve wide-field retinal imagingwith a camera that can be implemented as hand-held, that will image bothpediatric and adult patients, and that will have an optional built-inlight-weight image guided OCT and use a through the lens illuminationsystem that is free from or reduces glare and reduces or minimizesscatter. Embodiments can be used with seated patients.

According to a specific embodiment, a wide-field retinal imaging systemis provided that projects the retinal illuminating light through theimaging optics while obtaining high contrast, high resolution imageswith reduced or no glare from the imaging optics. Systems can beimplemented as hand-held or table-top systems that are useful for supineor seated patients. In some embodiments, an image-guided opticalcoherence tomography (OCT) system is integrated into the retinal imagingsystem.

Embodiments of the present invention address one or more of thefollowing issues:

Sensitivity to Scattering from the Eye Lens and Cornea

While children's crystalline lenses are in many instances verytransparent, this is not always the instance. Adult eye crystallinelenses become progressively less transparent with age and backscattering can reach large percentages.

Small Size, Weight and Appropriate Physical Configuration

The camera can be comfortably held by one hand so that the second handcan be used to hold the patient's head or for other functions. Thus, thephysical size is such that one hand can obtain a good grip on the camerabody and that the weight is not unduly stressful for the clinician. Inother embodiments, the camera can be mounted on a support.

No Visible Focused Ghost Images and Low Ghost Background

The light injection system does not produce “ghost” images (unwantedreflections from the optics, called “ghosts” because they are generallyof lower light level). And for ghost images that are not focal, thelevel of the ghost reflection is well below that of the retinal lightlevel.

High Resolution

Resolution of the optical system is high and meets or exceeds the ISOstandards for retinal cameras.

Wide-Field Imaging and Field of Regard to at Least the Equator

Wide-field imaging is provided so that much of the retina can becaptured with only a few images or an extremely wide-field single imagecan be obtained. Many of the clinical presentations in retinal carepresent wide-field such as diabetes, melanomas, retinopathy ofprematurity, and so forth. A field-of-regard (FOR) to the equator isalso provided.

Uniform Illumination

The irradiance on the eye should be uniform such that the variation ofimage brightness will be dominated by the regional reflectance of theretinal features and not the camera illumination pattern.

Efficient use of Illumination Light

Efficient use of illumination light means that LED light sources can beused, thus avoiding the issues of high temperature bulbs such as Halogenand the need for bulky and fragile fiber optic cables between a lightsource and the camera. Because of the efficiency of an LED, the LED canreside in the camera housing instead of the control box, eliminating thelarge fiber optic cable. Second, efficient collection of light alsomeans that the demands on the LED can be reduced.

Be Able to be Sanitized

The tip of the camera is contacted directly to body fluids and there isa risk of retaining pathogens that might be present in the patient'sbody. The system should be suitable for sanitation using common cleaningsolutions such as Alcohol and diluted bleach.

Insertion into Small Eye Sockets

With premature infants especially, the eye socket can be small. Thismeans that the camera tip should have a small diameter to reach to thecornea and for imaging to the periphery, it must be able to tip as well.

Addition of Image Guided OCT

OCT is a key technology for examining the layers of the retina and fordetermining the size of pathologies such as eye tumors. Being able toobtain OCT scans that are real-time image guided is a powerful tool andimportant dystrophies occur on a wide-scale in the retina such as forexample retinal detachments. The use of this tool should become veryprevalent in retinal surgeries.

To address these issues, embodiments of the present invention provide acamera that not only provides high-contrast and wide-field, butaddresses one or more of the issues discussed.

According to an embodiment of the present invention, a hand-held imagerfor imaging the retina of the eye is provided. The hand-held imagerincludes an illumination source operable to generate illumination lightand a beam splitter operable to receive the illumination light anddirect the illumination light along an optical axis. The hand-heldimager also includes a field lens disposed along the optical axis and anobjective lens disposed along the optical axis and operable to contactthe cornea of the eye. An aerial image is formed adjacent to the fieldlens. The hand-held imager further includes an image detector and one ormore lenses disposed along the optical axis between the beam splitterand the image detector. The one or more lenses are operable to form animage at the detector.

According to another embodiment of the present invention, a retinalimager for imaging a retina of an eye is provided. The retinal imagercan be hand-held or mounted on a support. The retinal imager includes anillumination source operable to generate illumination light and a beamsplitter operable to receive the illumination light and direct theillumination light along an optical axis. The beam splitter can bepolarized and/or can be a dichroic mirror. The retinal imager alsoincludes a field lens (e.g., a plastic asphere) disposed along theoptical axis and an objective lens disposed along the optical axis andoperable to contact a cornea of the eye. An aerial image is formedadjacent to the field lens. The aerial image can be non-chromaticallycorrected (i.e., characterized by chromatic aberration) and curved. Inone implementation, the field lens is disposed between the beam splitterand the objective lens.

The retinal imager further includes an image sensor and one or morelenses disposed along the optical axis between the beam splitter and theimage sensor. The one or more lenses are operable to form a sensor imageat the image sensor. The image sensor can be an array sensor. In someembodiments, the retinal imager can further include an OCT systemcoupled to the retinal imager.

According to yet another embodiment of the present invention, a methodof operating a retinal imager is provided. The method includespositioning the retinal imager adjacent the eye of the patient. Theretinal imager includes an illumination source operable to generateillumination light and an objective lens set including an objective lens(e.g., a single element objective lens) and a second lens. The methodalso includes bringing the objective lens in contact with a cornea ofthe eye and illuminating the retina of the eye with the illuminationlight passing through the objective lens set. The method furtherincludes reflecting at least a portion of the illumination light off ofthe retina to provide a return signal, directing the return signal alongan optical path, and detecting a sensor image at the image plane usingan image sensor.

According to a specific embodiment of the present invention, a method ofimaging a retina of an eye of a patient is provided. The method includespositioning a retinal imager adjacent the eye of the patient andobtaining a first image of a first portion of the retina, the firstimage associated with a central area (e.g., a circle) and a first fieldof view (e.g., 100 degrees). The method also includes obtaining a secondimage of a second portion of the retina, the second image associatedwith an annular area surrounding the central area. An outer periphery ofthe annular area is characterized by a second field of view (e.g., 130degrees) greater than the first field of view. The method furtherincludes combining the first image of the first portion of the retinaand the second image of the second portion of the retina to provide acombined image of the retina.

In one implementation, obtaining the first image of the first portion ofthe retina comprises operating a spatial light modulator to illuminatethe central area and block light propagating in the annular areasurrounding the central area. Obtaining the second image of the secondportion of the retina comprises operating the spatial light modulator toilluminate the annular area surrounding the central area and block lightpropagating in the central area. The spatial light modulator can belocated adjacent an image plane of an image sensor.

According to a particular embodiment of the present invention, a methodof forming a wide field of view image of a retina of an eye of a patientis provided. The method includes positioning a retinal imager adjacentthe eye of the patient and obtaining a first image of a first portion ofthe retina. The first image is characterized by central area and a firstfield of view (e.g., 100 degrees). The method also includes obtaining afirst additional image of a first additional portion of the retina. Thefirst additional image is characterized by a first azimuthal rangecovering a first portion of an annular area surrounding the centralarea. An outer periphery of the annular area is characterized by asecond field of view (e.g., 150 degrees) greater than the first field ofview.

The method further includes obtaining a second additional image of asecond additional portion of the retina. The second additional image ischaracterized by a second azimuthal range covering a second portion ofthe annular area surrounding the central area. Additionally, the methodincludes obtaining a third additional image of a third additionalportion of the retina. The third additional image is characterized by athird azimuthal range covering a third portion of the annular areasurrounding the central area. Furthermore, The method includes combiningthe first image of the first portion of the retina, the first additionalimage of the first additional portion of the retina, the secondadditional image of the second additional portion of the retina, and thethird additional image of the third additional portion of the retina toprovide a combined image of the retina.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is an optical schematic illustrating a classical through thelens illumination design.

FIG. 1B is an optical schematic illustrating a classical through thelens imaging design.

FIG. 1C is an optical schematic illustrating a classical through thelens illumination showing the effect of glare on the image.

FIG. 1D is an optical schematic illustrating a classical through thelens illumination showing the effect of scatter on the image.

FIG. 2A is an optical schematic illustrating delivery of light by meansof a fiber optic ring lying outside the receive optical path.

FIG. 2B is an optical schematic illustrating return of the retinalreflectance for the system illustrated in FIG. 2A.

FIG. 3A is an image profile of a grating at low spatial frequencies andhigh spatial frequencies.

FIG. 3B is a plot showing CTF functional dependence as a result ofoptical resolution alone.

FIG. 3C is an image profile of low and high spatial frequency gratingimages with scatter of 50%.

FIG. 3D is a plot showing a CTF function with and without scatter of50%.

FIG. 4A is an optical schematic illustrating a corneal contact throughthe lens illumination system with imaging.

FIG. 4B is an optical schematic illustrating a corneal contact throughthe lens retina camera showing illumination paths only.

FIG. 4C is an optical schematic illustrating a non-contact illuminationsystem.

FIG. 4D is an optical schematic illustrating the front of the eyeshowing pupils and illumination.

FIG. 4E is an optical schematic illustrating a cross section of acontact through the lens imaging system.

FIG. 4F is an optical schematic illustrating a through the lensillumination system showing issues of reflection from field lens withnegative curvature.

FIG. 4G is an optical schematic illustrating a through the lensillumination system showing issues of reflection from field lens withpositive curvature.

FIG. 5A is a corneal contact through the lens imaging system using asingle objective lens according to an embodiment of the presentinvention.

FIG. 5B is an optical schematic illustrating a corneal contact throughthe lens illumination system using a single objective lens according toan embodiment of the present invention including detail of a firstimage.

FIG. 5C is an optical schematic illustrating a corneal contact throughthe lens illumination system according to an embodiment of the presentinvention including details of a rear imaging system.

FIG. 5D is an optical schematic illustrating illumination optics of acorneal contact through the lens illumination system according to anembodiment of the present invention.

FIG. 5E is an optical schematic illustrating a corneal contact throughthe lens illumination system according to an embodiment of the presentinvention including details of illuminating optics.

FIG. 5F is an optical schematic illustrating illumination ray boundariesfor an eye of a first size according to an embodiment of the presentinvention.

FIG. 5G is an optical schematic illustrating illumination ray boundariesfor an eye of a second size according to an embodiment of the presentinvention.

FIG. 5H is an optical schematic illustrating use of an iris to blockouter rays according to an embodiment of the present invention.

FIG. 5I is an optical schematic showing additional detail of elementsillustrated in FIG. 5H.

FIG. 5J is a corneal contact through the lens imaging system using asingle objective lens according to another embodiment of the presentinvention.

FIG. 6A is an optical schematic illustrating an eye profile view of acontact through the lens illumination system with objective lens at 100degrees FOV according to an embodiment of the present invention.

FIG. 6B is an optical schematic illustrating a detailed anterior segmentview of a through the lens imaging system according to an embodiment ofthe present invention.

FIG. 6C is an optical schematic illustrating the concept of the “cone ofsilence.”

FIG. 6D is an optical schematic showing additional detail of elementsillustrated in FIG. 6C.

FIG. 7A is an optical schematic illustrating a through the lens imagingsystem with an extended FOV eye profile view.

FIG. 7B is an optical schematic illustrating a through the lens imagingsystem with an extended FOV anterior segment profile view.

FIG. 7C is an optical schematic illustrating a through the lens imagingsystem showing extended FOV of imaging but lower FOV of illumination.

FIG. 7D is an optical schematic illustrating a through the lens imagingsystem using a central image of a two image set to avoid the cone ofsilence.

FIG. 7E is an optical schematic illustrating a through the lens imagingsystem using a ring image of a two image set to avoid the cone ofsilence.

FIG. 7F is a schematic diagram illustrating imaging of a central imageaccording to an embodiment of the present invention.

FIG. 7G is a schematic diagram illustrating imaging of an outer ringimage according to an embodiment of the present invention.

FIG. 7H is a schematic diagram illustrating combination of the centralimage and the outer ring image according to an embodiment of the presentinvention.

FIG. 7I is a schematic diagram illustrating the use of a spatial lightmodular at a sensor according to an embodiment of the present invention.

FIG. 8A is an optical schematic illustrating a profile view ofillumination and imaging of an outer ring according to an embodiment ofthe present invention.

FIG. 8B is an optical schematic illustrating ultra-wide outer ringillumination and imaging using azimuthal segmenting as well as radialsegmenting according to an embodiment of the present invention.

FIG. 8C is a schematic diagram illustrating image segmenting at a sensoraccording to an embodiment of the present invention.

FIG. 9A is an optical schematic illustrating a compact OCT for hand-handimaging integrated with a hand-held imager according to an embodiment ofthe present invention.

FIG. 9B is an optical schematic illustrating details of an OCT beamtrain according to an embodiment of the present invention.

FIG. 9C is an optical schematic illustrating details of an OCT beamtrain according to another embodiment of the present invention.

FIG. 10 is a simplified schematic diagram illustrating a hand-heldimaginer for imaging the retina of an eye according to an embodiment ofthe present invention.

FIG. 11 is a simplified flowchart illustrating a method of operating ahand-held imager to image a retina of an eye of a patient according toan embodiment of the present invention.

FIG. 12 is a simplified flowchart illustrating a method of imaging aretina of an eye of a patient according to an embodiment of the presentinvention.

FIG. 13 is a simplified flowchart illustrating a method of forming awide field of view image of a retina of an eye of a patient according toan embodiment of the present invention.

FIG. 14A shows a plot of RMS spot size at the retina for the sensorimage at the image sensor according to an embodiment of the presentinvention.

FIG. 14B shows a plot of RMS spot size at the retina for the aerialimage according to an embodiment of the present invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

In eye retinal care there are many instances where imaging most of butnot necessarily all of the retina is sought. This is in contrast totraditional retinal imaging systems that typically only capture theposterior pole in a single image. One approach to achieve this is todevelop a retinal camera with an ultra-wide field-of-view (FOV). Thereare however substantial limitations with such imaging and these arederived especially from the physical size and shape of the anterior ofthe eye and issues related to scattering and glare. Very few dystrophiesare however present all the way to the ora serrati and cameras whichachieve a modestly wide FOV have great utility.

In addition, in babies, and even many older pediatric patients, fallinto the class of patients needing wide-field imaging but must be imagedsupine. Some adult patients, especially while in surgery, would benefitfrom an imaging system that could be hand-held and wide-field anduseable with the patient supine. Being able to mount such a system in amanner convenient for sitting patients would also be of value. Whilethere is a commercially available wide-field retinal camera designed forhand-held use for pediatric patients only, this system faces seriouslimitations with image contrast, especially in eyes where the retina isdarkly pigmented. Additionally, these systems, which may touch thecornea, will not work in a satisfactory manner with most adult patients.

In addition to classical bright field imaging and fluoresceinangiography, optical coherence tomography (OCT) has become the standardof care and is seen as of equal value to conventional imaging. Thispoints to the need for the provision of image guided OCT (where thebright field or angiographic image is displayed in real-time along witha marker on the image showing the location of the OCT scan). Embodimentsof the present invention utilize OCT in conjunction with a vastlyimproved hand-held wide FOV imager.

Embodiments of the present invention provide enhancements overconventional hand-held OCT cameras that do not simultaneously providebright field or angiographic imaging and have a heavy scan head.

The inventors have determined that while many physicians ask for“improved resolution” in many instances a better term would be “improvedvisibility.” Higher resolution can be used in the sense of theperformance of the optical lenses including the eye lenses to resolvetwo adjacent points. However, especially in the everyday clinic, thelimit to visibility is frequently contrast, not resolution. It isrelatively easy to design optics that on the ideal eye will have highresolution. It is, in comparison, very difficult to design illuminationinjection systems that deliver high contrast in the everyday clinic. Inthe clinic, on many occasions, only 80% of eyes image well, this limitarising from scatter in the human eye.

The level of difficulty of obtaining high contrast images of the retinacan be understood by considering the low level of return of retinalillumination back to the camera. Retinal reflectivity can be as low as10⁻³, the angular collection through the camera pupil is typically 10⁻³,giving a return of injected light of as low as 10⁻⁶ . In someimplementations, it is desirable to seek a total level of unwanted lightbelow 10⁻⁷.

In imaging systems where the light passes through the camera optics onthe way to the eye, the first challenge is to prevent unwantedreflections from the optics from entering the image. While this is notdifficult in classical non-contact table-top cameras, these do notprovide a wide FOV. These unwanted reflections are called “glare” or“ghost images.” With high performance anti-reflection coatings, thisreturn reflection is reduced to 5×10⁻³ of the outgoing light and butthis is a signal that can be much larger than the retinal return.Accordingly, the optical designer can use lens locations and curvaturessuch that the glare does not return to the image plane, especially as afocused or near-focused image, the so-called “ghost image”.Additionally, the light injection must be such that the irradiance willbe uniform on the retina and minimize scatter in the eye. For standardtable top retinal cameras avoiding glare can be accomplished, but at theexpense of narrow FOV and bulky size. However, in hand-held cameras thattouch the cornea, this requirement is difficult to meet.

These through the lens retinal cameras are comprised of two opticalsystems that share the same space and lenses; one injects theillumination and one receives the light from the retina and forms theimage. When OCT is integrated then three optical systems must generallybe considered and these also share some of the same optics. FIG. 1Aillustrates a classical through-the lens-illumination system. Lightsource 6 injects illumination 2 through beam splitter 5 and light iscollected by lens 3 and spread across object 1. Object 1 is a pattern ofreflective linear strips interspersed with dark strips. FIG. 1Billustrates the imaging system comprised of the object 1, thecollecting/imaging lens 3 and the typical return rays 7 are shown andform the image 4.

However, in this simplified optical system, neither glare nor scatter isconsidered. In FIG. 1C, glare is shown by optical rays 8 reflecting fromlens surface 10 and striking detector plane 4 causing a ghost image 9.In FIG. 1D, a scattering medium 11 is present and illustrative rays 12return to the image plane 4 causing a haze 14.

In imaging systems where the light passes around camera optics on theway to the eye, there is no glare, but the challenge is to preventunwanted back scatter to the image. This class of cameras was developedto achieve wide FOV and in particular to deliver illumination to theretinal periphery and all this in a hand-held form factor. FIGS. 2A and2B illustrate an around-the-lens illumination system. In thisillumination system, the illumination light is delivered through a fiberoptic bundle 15 surrounding the camera optics and specifically thecontact lens 234 such that there is no glare, but this approach facessubstantial challenges for uniformity of illumination and especiallyscatter 23. This system emphasizes the ability to direct light to theperiphery of the retina 20. However as seen in FIG. 2A, if the iris 17is not completely dilated, it can block the illumination rays 16 to thecentral portion of the retina 19, leaving a dark spot in the middle ofthe image. Since images are generally centered on the most interestingfeature, this has proven to be a major objection to this camera.

Also in FIG. 2B is shown the imaging optical paths for receipt of lightfrom the retina 21. Rays from the peripheral retina 20 exit through theentrance pupil 45 of the optical system and traverse first through thecontact lens 234 and then through additional lenses to the image plane.A ray from the central eye retina 19, if it is illuminated, would alsopass through the camera entrance pupil 45 and first through the contactlens 234 and then to the image plane.

However, as seen in FIGS. 2A and 2B, the eye crystalline lens 18contains many scattering centers, which back scatter 23 the illuminationlight back through the contact lens 234 and on to the image and thisserves as a key source of scattering that reduces image contrast in thisdesign. Also in FIGS. 2A and 2B, where both the illumination and receiveoptical systems are shown side by side a boundary 22 is drawn on bothimages delineating the volume in the lens 18 where both the outgoing andreturn light pass together. In this design then nearly all of the lightilluminating the eye passes through the crystalline lens 18 precisely insame volume 22 as the returning lights. From the viewpoint of reducinglens scatter, which is a major cause of low contrast images, such adesign creates the highest possible scatter 23 from the eye crystallinelens 18 possible. As a consequence, retinal cameras with around the lensillumination have been very unsuccessful at producing high contrastimages in a large percentage of pediatric patients and virtually alladult patients.

The inventors have determined that in many eyes the back scatteringfraction is of a sufficient percentage such that when it is multipliedby the high level outgoing light produces a scattering return 23 thatwhen compared to the low retinal return 21 destroys retinal contrast.Low contrast has a profound effect on the visibility of the key highspatial frequencies in the image. In this regard, for example,physicians want to detect tumors when they are small and a low contrastimage inhibits this.

Referring again at the simplified through the lens illumination systemoptical system of FIG. 1B, this is comprised of a lens 3, an object 1,which is a reflective grating, and an image 4, which is a replica of theobject subject to the imaging capability of the lens. In FIG. 3A, animage profile 24 is shown in which at low spatial frequencies the imagequality is very good, but at high spatial frequencies 25, the image isdegraded. This is of course driven by the imaging quality of the lens 3and the limits of diffraction. A quantitative measure of contrast is themodulation index is defined as

$m = \frac{\left( {{Ix} - {Im}} \right)}{\left( {{Ix} + {Im}} \right)}$

where Ix is the maximum intensity of the imaged pattern and Im is theminimum. This is a function of spatial frequency and is called thecontrast transfer function (CTF). As shown in FIG. 3B, the CTF 26declines with increasing spatial frequency f until it reaches a pointwhere the visibility of the grating disappears 28. A typical lowestvalue of m at which the grating cannot be observed is m=0.3. For a lowerquality lens, the plot might be 27 with a lower cut off frequency 29.While the CTF lines are show as straight for simplicity, they in generalexhibit a more complex shape.

While attention is rightly focused on the limits to the CTF sourced bylimitations of the optics, it needs to be recognized that scattering andthe like reduces contrast in a similar way. To see this we introducescattering as shown in FIG. 1D, where 11 is a volume containing materialthat scatters 12 and the scattered portion of the light at the image is14. FIG. 3C illustrates the new image of the grating at the higherspatial frequency 30 and low spatial frequencies 31, both withscattering included. Note however that the high spatial frequency shownnow has a modulation index m of 0.25, which falls below the visibilitycriteria of 0.3 and that at low spatial frequencies, the modulationindex never reaches 1.0. In FIG. 3D, the high scatter transfer function33 does not start at 1.0 and note that the cutoff frequency 32 is lower.The key issue is that the higher spatial frequencies are now notvisible. The CTF with scatter can be modified from the CTF withoutscatter. The retinal return as a fraction of outgoing light is R, theback scattering of the outgoing light is S, and Ix is the maximum of theCTF with no scatter and Im is the minimum of the CTF with no scatter,then the CTF will follow as:

$m = \frac{\left( {{Ix} - {Im}} \right)}{\left( {{Ix} + {Im}} \right) + {S/R}}$

Accordingly, if the CTF with no scatter was 1.00 at low spatialfrequencies and the backscatter was equal to the retinal return, thenthe CTF with scatter would be 0.5. And, when the backscatter was threetimes the retinal return, the CTF is reduced to 0.25 at low spatialfrequencies.

With the experience that around-the-lens cameras cannot by designreliably generate high contrast images of pediatric or seldom do so foradult patients, attention needs to be drawn to finding techniques toutilize through the lens illumination. Accordingly, embodiments of thepresent invention achieve wide-field retinal imaging with a camera thatcan be implemented as hand-held or table top, will image both pediatricand adult patients, and that will have an optional built-in lightweightOCT using a through the lens illumination system that is free from glareor reduces glare and reduces or minimizes scatter.

In addition to achieving high resolution and high contrast images,embodiments of the present invention achieve high FOV or highfield-of-regard (FOR). FOR is defined as the total accessible field ofimaging whereas field of view (FOV) is defined as the instantaneousangular field of the image. The simple means of tilting the imaging handpiece to direct the center of the image to different portions of theretina accesses the various instantaneous images which together form theFOR. In particular, however, it is not necessary to achieve ultra-wideFOV capture in a single image. What is needed is an efficient means tocapture a large amount of retina, but, if it were sufficientlyefficient, then, the use of multiple images montaged together would bean attractive solution. Additionally, if these objectives were to beachieved in real-time, then the profound limitations of post-clinicalsession montaging could be avoided. Achieving this would radicallychange ophthalmic imaging but would only be valuable if a wide FOR wasavailable.

Classical table-top based retinal cameras provide a field of view (FOV)of up to 60 degrees as measured from the entrance pupil. The efficientlyaccessed field of regard (FOR) is quite limited. A great deal of skilland patient cooperation is needed even for modest attempts at large FORimaging. Typically, classical systems are table top systems that are notsuitable for pediatric patients or supine adult patients.

Embodiments of the present invention meet the simultaneous challenges ofimaging supine patients, in high contrast and high resolution, in ahand-held imager, and at high FOR/FOV, while also providing angiographyand image guided OCT. Embodiments of the present invention are also ofhigh value with seated adult patients.

Some systems transmit light through the cornea, but outside the imagereceive optical path. However, the major disadvantage, and one thatprevents the use of this technology in many patients, is the lack ofhigh contrast imaging as the design teaches away from high-contrast. Akey feature of those designs is that light from one side of the eye isused to illuminate the retina on the opposite side, as shown in FIG. 2A.This is to allow illumination of the peripheral retina 20 perhaps not atthe key center of the image 19 where light can be blocked by the iris17. As for scattering the result is that the retina is indeedilluminated at the periphery of the field but the illuminating lightcrosses through the crystalline lens and through the volume 22 wherelight is returning from the retina to form an image. Thus, a great dealof the light passes through the crystalline lines in a volume 22 justposterior to the entrance pupil. The crystalline lens 18 is a majorsource of scattered light in the eye, in older patients this can be asmuch as 30% of the total light, and it is then collected with greatefficiency through the exit pupil of the eye and profoundly reduces theimage contrast. Thus, while this design eliminates the issues of ghostimages from the camera optics or crystalline lens optics, it suffersfrom the worst possible sensitivity to scattering from the crystallinelens.

Indeed this device is seldom useful for adult patients since as the eyeages the crystalline lens develops more scattering centers. And, somepediatric patients have a lot of scattering from the crystalline lensgiving a very low contrast image. Since some patients have dark retinaswith a reflectivity over ten times below that of brightly pigmentedretinas, the scattering is sufficiently high that these patients cannotbe effectively imaged.

In contrast, embodiments of the present invention provide a wide-fieldretinal imaging system that does not suffer from ghost images ormeasurable contrast reducing scatter and produces quality images ofpatients with even darkly pigmented retinas, older eyes, or pediatriceyes with diseases that cause large increases in scattering.

Optical coherence tomography (OCT) is used to observe and documentlayers in the eye, tumors, and the like. The OCT scan is conducted usinga low coherence optical source operating in the near infrared, whichtherefore is not visible to the eye. To circumvent this limitation,designers have resorted to acquiring a three-dimensional image, storingit, and then allowing the clinician to scan through the OCT image postimaging. This still does not give direct clues for the precise locationof the 3D feature on the color retinal image. In contrast, embodimentsof the present invention provide a real-time OCT scan location from thebright field, which is of enormous clinical value.

Embodiments of the present invention avoid scattering and glare usingthrough the lens illumination, utilizing a through the lens hand-heldwide-FOV retinal camera that produces high-contrast images of pediatricand adult patients and has a built-in image guided OCT and is lightweight.

Glare: the Problem

FIGS. 1A-1D discussed above addressed the generic issues of through thelens illumination systems. In a through the lens illumination system,glare from the camera lenses, the cornea, and the crystalline lens mustbe considered. FIG. 4A illustrates a through the lens contact imagingsystem using a classical contact imaging design. The object is to forman image 42 of the retina 13 onto the array sensor 43. The objectivelens group 35 forms the first image 37. In the objective lens group 35there is a triplet, a doublet, one singlet lens and a field lens 39. Theobjective lens group 35 forms a quality image at 37 so that the relaylens group 38 will deliver quality images 42 with any objective lensgroup 35. Objective lens groups with ultra-wide FOV and highmagnification can be provided accordingly and interchanged.

Rear lens set 38 performs three key functions. First, it reimages theintermediate image 37 to the rear image 42 located at array sensor 43.Second, the relay lens group 38 provides focusing for the camera. Third,the rear lens group 38 has a Lyot stop 41 that is reimaged to the eyeentrance pupil located at plane 44 and that forms the camera entrancepupil 45 (not shown here).

FIG. 4B illustrates a more detailed cross section of a through the lensillumination system, particularly the illumination paths. Light source 6is injected by lens 50 through an annular mask 51, then through a beamsplitter 5 and finally through the objective lens set 35 the (thecomplex paths of rays through 35 are not shown) and to the retina 13.The annular mask 51 is focused near the eye pupil plane 44 and diverges48 to fill the eye.

FIG. 4C illustrates a cross section of a non-contact through the lensillumination system according to an embodiment of the present invention.The cross sectional view in FIG. 4C shows the relayed image of theannular mask 49 (a ring of light), which then expands 48 to illuminatethe retina 13. The light returning from the retina 13 is bounded byreturn rays 47 and passes through the entrance pupil 45 of the camera(the image of the Lyot stop 41 and on to the image sensor 43, which canalso be referred to as an array sensor since it can be implemented usinga CCD or another appropriate imaging device. Note that region 58 is avolume of space in front of the cornea 59 for which the illuminationlight directed to all parts of the eye comes into a small bundle withintense irradiance, especially in the conical volume 36.

FIG. 4D shows the front view of the eye in which 53 is the edge of thecornea, 49 is the annular light ring, 52 is the diameter of the eyepupil and 45 is the entrance pupil for the camera. FIG. 4E illustrates across section of a through the lens illumination system with a contactlens 434 in place. The illumination boundary rays 48 are shown and thefront surface 56 has an intense illuminance, especially on the frontsurface 56 of contact lens 434. This intense irradiance at this lenspresents a major challenge for corneal contact through the lensillumination systems due to reflections from the surface 56. As anexample rays 55 are reflections from the front surface 56 of the contactlens 434.

The large ratio between outgoing and return illumination presents yetanother challenge for glare in hand-held corneal contact retinalcameras. FIG. 4F illustrates the optical train of a classical throughthe lens illumination system and highlights issues of reflection fromthe field lens. In FIG. 4F, the last lens 39 in the objective lens set35 is shown along with the rear lens set 38. This lens 39 at leastpartly serves the function of a field lens. A field lens sits at or nearthe focus and contributes little if any power to the system but directsthe image rays into a small cone so that the rear lens set 38 can be ofa smaller diameter. This is critical as the image 42 can be large andthe return cone is highly divergent and without this, the rear lenseswould have to have a physically large diameter. The rear lens set thenin order to maintain reasonable f numbers would require a much largersize in terms of length.

However design principles for this system demand that this lens needssurfaces curved towards the image sensor 43. (While several lenses havethis curvature and create problems, this one is especially troublesome.)Note in FIG. 4F, the ghost refection from the first surface of 39directs ray 57 through the Lyot stop 41 and on to a ghost image at 42.

FIG. 4G illustrates the optical train of a through the lens illuminationsystem and highlights issues of reflection from a reversed field lens.In FIG. 4G, lens 39 has been turned around for illustration,demonstrating the point that the lens surface curvatures now in 39creates a refection 57 whose diameter is very large. The Lyot stopblocks most of this and the irradiance per pixel at image sensor 43 issmall and potentially non-significant. Clearly lenses with curvaturessuch as shown in FIG. 4F will create a significant dilemma foreliminating ghosts.

Referring once again to FIG. 4A, which shows the classical contactimaging lens format, fourteen reflective surfaces are illustrated:

The back of the eye crystalline lens

The front of the crystalline eye lens

The cornea, both surfaces

The contact lens

The bonded interface in the first bonded triplet

The rear glass to air interface of the first triplet

The front air to glass interface of the second doublet

The bonded interface of the second doublet

The front air to glass surface of the second doublet

The first air to glass surface of the singlet

The second air to glass surface of the singlet

The first surface of the field lens

The second surface of the field lens.

The need for a large number of optics for a quality image arises fromthe low optical quality of the human eye. While the resolution is highon axis (where reading occurs) towards the periphery, the resolution isvery poor. And, the eye is not chromatic, the brain uses thelongitudinal chromatic aberration to assist in focusing and the brainassembles the image in high quality. Thus, the camera designer is forcedto use a substantial number of optics for high quality wide FOV imaging.As a result of the large number of optical surfaces, it is challengingor impossible to develop a solution characterized by no or reducedghosts, uniform irradiance on the retina, and also high contrast.

Accordingly a first design principle utilized by embodiments of thepresent invention is that the number of lenses for which theillumination light is passed through will be reduced or minimized andthat these surfaces will have the preferred curvature to prevent focusedghost images. This design principle lies in conflict with therequirement for high resolution images, uniform irradiance and a qualityfirst image.

In order to accommodate the conflicting requirements for absolutely noor faint non-focused glare in a through the lens illumination system forwide FOV hand-held retinal imaging a new design concept has beenimplemented by embodiments of the present invention. If the issues ofglare, especially for any lens close to the eye can be completely andabsolutely removed, the design space for resolution, compactness, andillumination uniformity will be vastly enlarged.

Classical optical paradigms for design include an objective lens setthat is required to produce a high quality image. Among other designprecepts, it is taught in general optical design that the optics shouldnot allow the red, green and blue rays to diverge in angle or ray heightfor any significant distance. The further into the beam train theseproceed without correction the harder it is to put them back together.Note also that images must be flat to be applied to array sensors. Theclassical paradigms are seen evident in telescopes and microscopes.

Glare: the Solution

Embodiments of the present invention utilize a design concept thatdiffers from conventional optical design precepts. FIG. 5A illustrates acorneal contact wide-field imager according to an embodiment of thepresent invention. In the embodiment illustrated in FIG. 5A, a highresolution corneal contact wide-field imager is implemented with theunusual use of only one objective lens 510. This objective lens 510 doesnot have any surfaces negative towards the illumination source as theyare objectionable for causing focused ghost images. The first image 514,which can be referred to as an aerial image, is shown as not achromatic,not high resolution, nor flat.

FIG. 14A shows a plot of RMS spot size at the retina for the sensorimage at the image sensor according to an embodiment of the presentinvention. FIG. 14B shows a plot of RMS spot size at the retina for theaerial image according to an embodiment of the present invention.Referring to FIGS. 14A and 14B, the RMS spot radius on the retina at thefirst image plane (where the aerial image is formed) as a function offield angle is shown in FIG. 14B. Retinal image resolution requirementsare identified in ISO 10940 and these are noted on the plot as shortdark horizontal lines and numbers are given from the central field, themid-peripheral field, and the far peripheral field. For example, forwide field in the center of the image, the specification is 60 lp/mm ora spot size of 8 microns. At the edge, the requirement is 25 lp/mm or aspot size of 12 microns.

In all locations, the aerial image 514 fails to meet the standards ofISO 10940 by a large margin. By comparison, the image of the retina atthe image sensor 562 (i.e., the detector) greatly exceeds therequirements as shown in FIG. 14A. Thus, the image quality of the sensorimage at the image sensor, defined, by example, by ISO 10940, is greaterthan the image quality of the aerial image.

Indeed, as shown in FIG. 5B, the aerial image includes a tangentialimage 516 in FIG. 5B) and the sagittal image 518 in FIG. 5B) havemillimeters or more of curvature at the edge and in differentdirections. Referring to FIG. 5A, the objective lens 510 (which can bethe sole or only objective lens) utilized in the illustrated embodimentcaptures the light reflected from the retina 13, directing it in thedirection of the image sensor 562, which can also be referred to as animage capture array, but not producing ghost images. The second lens512, also referred to as a field lens, serves in part as a field lensand in part for image correction and is located within the illuminationlight 505 provided by an illuminator, also referred to as anillumination source (not shown).

Referring once again to FIG. 5A, the optical elements downstream of thebeam splitter 520 can be referred to as an imaging lens group 540. Someof these optical elements are described in relation to FIG. 5C below.Beam splitter 544 is utilized to receive IR light from the optional OCTsystem and to transmit light to the OCT system. Thus, the OCT path isillustrated as optical path 507 in FIG. 5A.

Thus, embodiments of the present invention result in no or a reducedrequirement placed on the quality of the first or aerial image. The highdegree of optical correction is left to the rear optics lens set (i.e.,imaging lens group 540), a concept either not recognized or believed tobe not realizable. Note that embodiments of the present invention use 11lenses (an achromatic is counted as two lenses) vs. conventional designsthat can use 12 lenses. Accordingly, while embodiments teach away fromstandard design theory, these present embodiments illustrate that it isfeasible and even with fewer lenses.

FIG. 5B illustrates the details of the objective lens set for thecorneal contact wide-field imager shown in FIG. 5A. Rays 511 returningfrom the retina and through the object lens 510, which can be a contactlens, then pass through the second lens 512. These lenses could also beaspheric lens. Image 516 is the tangential image and 518 is the sagittalimage. These images are each curved over a millimeter at the edge,giving over a 2 mm edge separation. By any standard, this is barelyclassified as imaging and the lenses 510 and 512 can be consideredmerely a light collection system rather than an imaging system. Notshown are the red, green and blue images, also lying in different focalstructures.

In FIG. 5C is shown details of the rear optics of the imaging system.Several of the optical elements illustrated as part of the imaging lensgroup 540 are illustrated in FIG. 5C. Lens 548 lies anterior to theillumination path and none of these lenses are subject to producingglare. The Lyot stop 570 lies just in front of the focusing lens 572,which forms the final and high quality image at an image plane 560,which lies in an image plane of an image sensor 562. Design codessuggest resolution at 3 microns and this is considerably improved overother wide-field cameras. Although only optical elements downstream ofthe beam splitter 544 are illustrated in FIG. 5C, it will be appreciatedthat other optical elements, including lens 542 can be utilized in theimaging lens group 540.

The detailed illumination format that is shown in FIG. 5D is a ringsource but second lens 512 is far enough from the cornea that it avoidsbeing in the region of high intensity illuminance 58 in FIG. 4C) infront of the cornea. In fact is it is close enough to the light ringsource 51 that there is no illuminance at the apex 513 of the secondlens 512, greatly aiding the prevention of ghosts. There is no glarereturned to the image plane 560 by second lens 512, the objective lens510, the cornea 508, or the eye lens (18 in FIG. 2A). Accordingly,embodiments of the present invention as illustrated in FIG. 5A can becharacterized by no glints while producing wide-field illumination.

Referring once again to the illumination system shown in FIG. 5D, lightsource 126, which can be an LED, has a finite area and the light isfirst intercepted by mask 125, which contains a single block in themiddle. The light is then intercepted by mask 51, which has an annulusopening to be imaged to light ring 49 in FIG. 6A). Lens 106 a doubletand doublet lens 113 constitute the illumination projection system. Item127 is an optional excitation filter for angiography. Return light fromthe retina is intercepted by beam splitter 520. Second lens 512 andobjective 510 also play a role in delivering light to the appropriatearea the retina 13 with a high degree of uniformity of illuminance.

In FIG. 5E is shown a more detailed description of the front end of theillumination system. The illumination system produces uniformilluminance at the retina 13 when the diameter of the eye is known usinglens 124 and lens 123 as well as other optical elements. For example asshown in FIG. 5F if the system is designed for the eye of the sizeillustrated in FIG. 5F, then the illumination rays boundaries 48 willjust meet at the center 131 of the retina. However, as shown in FIG. 5G,if a larger diameter eye is present, then the rays 48 from both sides ofthe retina will overlap at the center 131 giving an irradiance “hotspot.” This can be avoided by placing an iris at location 132 that canbe set to block the outer rays 134 of the illumination bundle andtherefore block the inner rays 133 at the retina. This is shown in moredetail in FIGS. 5H and 5I.

FIG. 5J is a corneal contact through the lens imaging system using asingle objective lens according to another embodiment of the presentinvention. The system illustrated in FIG. 5J shares common elements withthe system illustrated in FIG. 5A and the description related to FIG. 5Ais applicable to the system illustrated in FIG. 5J as appropriate. InFIG. 5J, an additional field lens 592 has been added between the secondlens 512 and the beam splitter 520. In the illustrated embodiment, theadditional field lens 592 is positioned between the aerial image 514 andthe beam splitter 520.

The utilization of the additional field lens 592 extends the distancebetween the second lens 512 and the beam splitter 520, which lengthensthe grip 1040 illustrated in FIG. 10, making the hand-held imager easierto hold in a user's hand. Moreover, additional optics may be usedwithout significant introduction of glare since the illumination beam inthis region is a ring and easily reflects off the curved section of thelens to the walls of the camera, not entering back to the image plane.One of ordinary skill in the art would recognize many variations,modifications, and alternatives.

Scatter/Contrast: the Solution

The main sources of haze are scattering from the crystalline lens andthe cornea and these backscatter at significant levels. In the humaneye, the crystalline lens and the cornea have nominally equal backscattering per cubic mm. The cornea, while 200 μm thick, tends to backscatter more blue light. The crystalline lens may be as much as 2,000 μmthick, but, it will have proportionally less blue light scatter. Bluelight scatter is the most significant challenge as this is dominated byRayleigh scattering, which intensifies with the inverse fourth power ofthe wavelength. This scatter grows with patient age and this is why someretinal imaging systems are not applicable to adult patients.

FIG. 6A illustrates a cross section of the eye in a through the lensilluminations system using one objective lens according to an embodimentof the present invention. It should be appreciated that a clear gelincluding methocellulose, such as Gonak or Goniovisic, can be utilizedbetween the contact lens and the cornea.

FIG. 6A shows the objective lens 510, the cornea 508, the eyecrystalline lens 18, the camera entrance pupil 45, and the illuminationring 49. The input illumination bounded by rays 48 illuminates theretina 13 up to the point 64 which is at 100 degrees as measured fromthe center of the eye and the light is returned as bounded by rays 47,illustrated as rays 511 in FIG. 5B. The entrance pupil 45 of the imagingsystem is positioned between the lens 18 and the cornea 508. Theillumination ring 49 is positioned at the front of the lens 18, parallelto the iris. Thus, the entrance pupil 45 of the imaging system and theillumination ring of the imaging system are offset longitudinally. In anembodiment, the longitudinal offset ranges from about 1 mm to about 5mm, for example, 3 mm. The offset between the pupil and the illuminationring may allow designers additional margin when seeking to avoid theincoming light 48 from crossing an area when there is scattering tissueand the light can scatter back into the beam 47.

FIG. 6B shows a magnified image of the anterior segment of the eyeillustrated in FIG. 6A. The input illumination light is bounded by rays48, the return light is bounded by rays 47, and the major scatteringmedia the cornea 508 and the lens 18 are shown. The inventors have notedthat the return rays delineated by rays 47 do not share the same spaceas the incoming rays delineated by 48 in the region of the cornea 508 orcrystalline lens 18. Also, note the non-intersection area as marked bycircles denoting volume 60 at the lens 18 and volume 61 at the cornea508. This enables embodiments of the present invention to achieve areduced amount of scattering or the lowest possible scattering.

In order for the scattering of the lens or cornea to enter into theimage, the scattering centers must lie in the paths of the return light,which is not present in this design. The image produced by such a designwill not be degraded by scattering in the cornea 508 nor the crystallinelens 18. It should be noted that the entrance pupil 45 and theillumination ring 49 are not located in precisely the same plane, butslightly offset longitudinally. By offsetting the illumination ring 49and the camera entrance pupil 45 it is possible to achieve no scattingin the return light path 47 from either the cornea 508 or the lens 18.If the entrance pupil 45 was pushed anterior to lie in the iris planewith the illumination ring 49, then there would be scattering from theeye lens 18 and the cornea 508. If the entrance pupil 45 were pushedanterior, then there would be scattering from the lens 18. Indeed, manyretinal images have an intense blue haze at the edge of the image.

FIG. 6C is a schematic diagram illustrating cones formed by light raysaccording to an embodiment of the present invention. FIG. 6C illustratesthe cones of light above 70 and below 72 the entrance pupil 45. Theinventors term this as the “cone of silence.” According to embodimentsof the present invention, a high contrast design is provided that doesnot place any illumination light in the cone of silence crossing anyhigh scatter media 73 and 71.

First solution to scatter/contrast while imaging nearly the entireretina: high field of regard

For wide-field cameras, the best measure of FOV would be from the centerof the eye. The covered retinal surface area scales with the square ofthe FOV as measured from the center of the eye whereas the coveredretinal area has a non-linear relationship with the FOV measured fromthe entrance pupil. By this measure the FOV of the design shown in FIG.6A is 100 degrees.

It has been common in ophthalmology for about fifteen years to inpost-acquisition form montages of images obtained at different lookangles. The technology for this has gradually improved but this is stilla tedious task and is nearly always performed by ophthalmic technicianswith a lot of training and rarely if ever by a physician. However,post-acquisition is always difficult as when obtaining a large set ofimages the clinician cannot typically determine if the set is good untilleaving the presence of the patient. Indeed, this kind of work isusually accomplished by technicians at the end of the clinic day, goodresults are not frequently the case.

In contrast with these conventional systems, embodiments of the presentinvention form a mosaic of images in real-time as they are obtained. Theimages can be automatically obtained and merged on the fly or the usercan provide an indication (e.g., press a button) when the best image ateach look angle is obtained. Using this method, embodiments of thepresent invention provide revolutionary solutions for ophthalmicimaging.

According to the embodiments described herein, the FOV can be extendedwith perfect or near perfect rejection of scatter from the cornea andlens by obtaining segmented images in rapid succession.

Second Solution to Scatter/Contrast: Wider Field Images

However, wider FOVs are sought and attempting to just open up the FOV asshown in FIG. 7A leads to overlap of the incoming and outgoing light,violating the principle of the “cone of silence.” Shown in more detailin FIG. 7B there is overlap in the lens 18 in volume 60 and the cornea508 in volume 61. Likely the periphery of the image will be hazy andfrequently retinal cameras have a blue tinged periphery.

FIG. 7C illustrates a cross section of the illumination/imaging systemwhen the FOV is opened to 130 degrees, point 65 on the retina (asillustrated in FIG. 7A) as opposed to 100 degrees, point 64 on theretina. In this instance the illumination field has not been increasedand remains at 100 degrees, return rays 47 even though imaging is openedup to 130 degrees.

A solution to this violation of the cone of silence is shown in FIGS. 7Dand 7E. The system is constructed such that the FOV and field ofillumination can be delivered at 130 degrees. Then the system will beset to obtain and merge two images, according to techniques, protocols,and means disclosed below. Referring to FIG. 7D, a first image asobtained that is constricted temporarily to 100 degrees at the sensorand the retina illuminated also to 100 degrees. This produces the sameimage as the system shown in FIG. 6A. This is accomplished as shown inFIG. 7I by using a spatial light modulator 710 located adjacent or atthe image plane 560 and intercepting the light 69 just before the imagesensor 562.

The CCD shutter is opened and left open during this process so that anyand all images will be collected by the array sensor. As shown in FIG.7F, which is a face on image of the array sensor for the imagingcondition illustrated in FIG. 7D, an image of a first central area 720is formed in the central area, which can be circular. The central area720 associated with the first central image is characterized by a firstfield of view, for example, 100 degrees. An outer ring or annular area730 is not imaged. The outer periphery 734 of the annular area 730 ischaracterized by a field of view of 130 degrees. The central area 720and the annular area 730 are contiguous since the periphery of thecentral area forms a common border with the inner periphery of theannular area. The alignment of the central area and the annular area inthe image plane is also present in the object plane on the surface ofthe retina, providing a first image of a central area of the retina anda second image of an annular area of the retina that surrounds and iscontiguous with first image of the central area. One of ordinary skillin the art would recognize many variations, modifications, andalternatives.

Then the spatial light modulator is closed for the central area 720 ofthe first central image and opened to image the annular area 730, whichcan also be referred to as an outer ring. Then as shown in FIG. 7E thereis illumination provided, system discussed below, in a ring of light 75on the retina between the first field of view (e.g., 100 degrees) andthe field of view of the outer periphery 734 of the annular area 730(e.g., 130 degrees) and the returning light 74 is also in a ring. Thus,a second image of a portion of the retina is formed as shown in FIGS. 7Dand 7G, with the retina illuminated in a ring bounded by rays 75 and thelight is received also in a ring bounded by rays 74. Note now that thereis no violation of the cone of silence at 60 or at 61 as illustrated inFIG. 7E. Accordingly, both the first image of the central area 720 andthe second image of the annular area 730, also referred to as aperipheral area, are free from scatter and the image sensor accumulatesboth the first image of the central area 720 and the second image of theperipheral area 730 to provide a final combined image as shown in makefinal image as shown in FIG. 7H. As discussed above, although FIGS.7F-7H show central and annular areas in the image plane, correspondingareas in the object plane (i.e., the retina) will be present and thediscussion associated with the image plane is applicable to the objectplane as appropriate.

Other embodiments use a CCD that is equipped to obtain one image, thenconduct a rapid frame transfer to external memory, and then acquire asecond image. Such a sensor can be used to capture these images and thenthe external scatter in the first image outside the first field of view(e.g., 100 degrees) could be removed digitally. These sensors are of theinterline class and are frequently used for particle image velocimetry(PIV) applications and time between frames can run as low as 80microseconds.

Third Solution to Scatter/Contrast: Ultra-Wide Field Images

To open up the FOV to 150 degrees, a more complex segmented imagingprocess can be utilized according to an alternative embodiment. Asdiscussed above, the central image of the central area of the retina(e.g., an image with a field of view of 100 degrees) can be the firstimaging step, but the imaging of the annular area of the retina (i.e.,outer ring) is characterized by a wider field of view (e.g., anadditional 22.5 degrees of width instead of 15 degrees) and a morecomplex system is employed for imaging of the outer ring.

FIG. 8A is illustrates a profile view of an eye including illuminationand imaging of an outer ring according to an embodiment of the presentinvention. As discussed above, the first image of the first portion ofthe retina is obtained at a first field of view (e.g., 100 degrees) andin FIG. 8A, only the outer ring is depicted. The portion 814 of theretina is illuminated in an annular manner, with portion 814representing a radial line extending across the annulus, enablingimaging of the outer ring. The outer illumination ring bounded by rays810 now covers the retina with a width of 22.5 degrees on each side ofthe first (i.e., central) image. As a result, the injected light for therays 810 on the outer periphery of the outer ring will intersect withthe returning light illustrated by rays 812 in volume 61 located at thecornea even though it does not in volume 60 located at the lens of theeye. However, the intersection with incoming and outgoing light involume 61 at the cornea occurs from the opposite side of the retina.

FIG. 8B illustrates ultra-wide outer ring illumination and imaging usingazimuthal segmenting as well as radial segmenting according to anembodiment of the present invention. As shown in FIG. 8B, by limitingthe azimuthal dimension of the ring, the intersection between incomingand outgoing light from across the retina can be avoided.

In the profile view of the eye illustrated in FIG. 8B, illumination andimaging of an outer ring are shown over an azimuthal segment making up aportion of the annular ring. As discussed above, the first image of thefirst portion of the retina is obtained at a first field of view (e.g.,100 degrees) (i.e., a central image) and in FIG. 8B, only the outer ringis depicted. The outer illumination ring bounded by rays 820 now coversthe retina with a width of 22.5 degrees on each side of the first (i.e.,central) image. The injected light is represented by rays 820 on theouter periphery of the outer ring and the return light is represented byrays 822. A portion 824 of the retina represents a radial line extendingacross the azimuthal segment of the annular ring.

FIG. 8C illustrates a view from along the optical axis of azimuthalsegments according to an embodiment of the present invention. In FIG.8C, a three quadrant version with azimuthal segments 830, 832, and 834and central area 720, also referred to as a central segment, isillustrated, with the azimuthal segments being illuminated in sequenceand with the appropriate masking in some embodiments. Referring to FIG.7F, peripheral area 730 has been divided into azimuthal segments and thewidth of the peripheral area has been increased from 15 degrees to 22.5degrees, although other widths can be used. The additional field of viewwidth is illustrated by width w in FIG. 8C, for example, 22.5 degrees,although other additional widths can be utilized. The central image ofthe central segment 720 of the retina is thus obtained and combined withthe azimuthal images of the outer ring of the retina (azimuthal segments830, 832, and 834) to form a combined image of the retina.

Although three quadrants with a first azimuthal range (i.e., 0-120degrees), a second azimuthal range (120-240 degrees), and a thirdazimuthal range (i.e., 240-360 degrees) is illustrated in FIG. 8C, thepresent invention is not limited to this particular implementation. Inother implementations, fewer azimuthal ranges are utilized (e.g., twoazimuthal ranges) or additional azimuthal ranges are utilized (e.g.,four or more azimuthal ranges). Additionally, although the increase infield of view of an additional width of 22.5 degrees is illustrated inFIG. 8C, the present invention is not limited to this particular widthand other additional widths are included within the scope of the presentinvention. One of ordinary skill in the art would recognize manyvariations, modifications, and alternatives.

As stated above, embodiments of the present invention provide greatclinical advantage via the addition of OCT to the hand-held imager andcontrast with conventional systems that are heavy, have narrow FOVs, arein general hard to use, and do not have a bright field or fluoresceinangiography built in. Some current systems obtain an image in threedimensions over a square, two-dimensional area of the retina and savethis data. Then the en face OCT data is displayed in two dimensions(e.g., x and y) with a separate color line over the upper part of thisimage. This line scans slowly downward while simultaneously displayingthe two dimensional OCT data (e.g., x and z). While this gives theclinical data on the layers in the retina, there is a great difficultyin locating the OCT data on the bright field. Thus, to address theseshortcomings, embodiments of the present invention present the lineindicating the location of the OCT x-z data on the real-time brightfield. A plurality of lines can be utilized to provide 3D data. One ofordinary skill in the art would recognize many variations,modifications, and alternatives.

FIG. 9A is a schematic diagram illustrating a hand held imager withintegrated OCT according to an embodiment of the present invention.Referring to FIG. 9A, the OCT optical chain is illustrated that would beutilized in imaging a retina. Imaging lens group 540 is the segment ofthe system at the rear portion of the imaging system, portions of whichwere described in relation to FIG. 5C. The objective lens set 501 isillustrated as well and the optional OCT return/transmit segment 910. InFIG. 9B, details of the OCT imaging/transmit section 910 areillustrated. There is an image at focal point 920 and a single fibertransmitting/receiving the OCT light to and from the OCT engine. Lens918 projects the IR light forward and there is a pupil 916 at MEMSmirror 917. Lens 914 and lens 912 project the IR light towards beamsplitter 544, which reflects the IR light into the optical system of thecamera.

In an embodiment, the software that is used to send the x and y signalsto the MEMS mirror 917 also provides data to the display for adding anindication line to the bright field data. It will be appreciated thataberration correction, both at visible and IR wavelengths is providedsuch that the OCT image resolution requirements are met by the rearoptics in FIG. 9A.

FIG. 9C is an optical schematic illustrating details of an OCT beamtrain according to another embodiment of the present invention. Thesystem illustrated in FIG. 9C shares common elements with the systemillustrated in FIG. 9B and the description related to FIG. 9B isapplicable to the system illustrated in FIG. 9C as appropriate. In theOCT system illustrated in FIG. 9C, there is an image at focal point 920and a single fiber transmitting/receiving the OCT light to and from theOCT engine. IR light is projected toward MEMS mirror 917. Lens 932 andlens 930 project the IR light towards beam splitter 544, which reflectsthe IR light into the optical system of the camera.

FIG. 10 is a simplified schematic diagram illustrating a hand-heldimager for imaging the retina of an eye according to an embodiment ofthe present invention. The hand-held imager 1000 includes a housing 1002that encloses one or more of the optical elements described herein.Referring to FIG. 10, the hand-held imager 1000 is placed adjacent theeye 1010 that is to be imaged. The objective lens set 501, includesoptical elements including the objective lens 510 and the second lens512 illustrated in FIG. 5A. The illuminator 1020, also referred to as anillumination source, provides the illumination light 505 illustrated inFIG. 5A. The beam splitter 520, directs the illumination light 505toward the objective lens set 501.

Light reflected from the eye passes through the objective lens set 501in the return path, passes through beam splitter 522 and is imaged usingthe imaging lens set 540 to form an image at image plane 560 associatedwith the image sensor 562. An optional OCT return/transmit segment 910,can be mounted on an outer surface of housing 1002 in some embodiments.In other embodiments, the OCT segment can be disposed in the housingalong with other optical elements and segments. A grip 1040 is providedsurrounding the objective lens set 501 to enable a user to hold thehand-held imager in their hand. Typically, the length of the grip is onthe order of 6 inches to facilitate holding of the hand-held imager bymedical personnel.

In some embodiments, the illuminator or illumination source 1020, theobjective lens set 501, and the imaging lens set 540 are disposed insidethe housing, providing a compact package suitable for hand-held use.Power and communications are provided to the hand-held unit throughpower/communications cable 1050, which can be connected to the housingat input/output connector 1052.

According to an embodiment of the present invention, a hand-held imagerfor imaging a retina of the eye is provided. The hand-held imagerincludes a housing. A number of optical elements are disposed in thehousing including an illumination source operable to generateillumination light and a beam splitter operable to receive theillumination light and direct the illumination light along an opticalaxis. An objective lens set is disposed along the optical axis andincludes a field lens disposed along the optical axis and an objectivelens disposed along the optical axis and operable to contact a cornea ofthe eye. An aerial image is formed adjacent to the field lens. Alsodisposed in the housing are an an image sensor and one or more lensesdisposed along the optical axis between the beam splitter and the imagesensor. The one or more lenses are operable to form a sensor image atthe image sensor.

In one use case, the hand-held imager is held in the hand of a user foruse during retinal imaging. In another use case, the patient's head issupported in a chin-forehead rest and the hand-held imager is mountedadjacent the chin-forehead rest. Thus, the use of the term hand-held isnot intended to limit the scope of the present invention to only beingheld in a user's hand, but to include applications in which the retinalimager is mounted. One of ordinary skill in the art would recognize manyvariations, modifications, and alternatives.

FIG. 11 is a simplified flowchart illustrating a method of operating ahand-held imager to image a retina of an eye of a patient according toan embodiment of the present invention. The method 1100 includespositioning the hand-held imager adjacent the eye of the patient (1110).The hand-held imager includes an illumination source operable togenerate illumination light and an objective lens set including anobjective lens and a second lens. The objective lens can be implementedas a single element objective lens in some embodiments. In someembodiments, the second lens serves as a field lens. The method alsoincludes bringing the objective lens in contact with a cornea of the eye(1112) and illuminating the retina of the eye with the illuminationlight passing through the objective lens set (1114).

The method further includes reflecting at least a portion of theillumination light off of the retina to provide a return signal (1116),directing the return signal along an optical path, (1118), and detectinga sensor image at the image plane using an image sensor (1124).

In some embodiments, the method also includes forming an aerial imagealong the optical path at an aerial image location adjacent to the fieldlens (1120) and forming the sensor image at an image plane by imagingthe aerial image (1122). In these embodiments, the aerial image ischaracterized by a first image quality and the sensor image at the imageplane is characterized by a second image quality higher than the firstimage quality. As an example, the aerial image can be characterized bychromatic aberration that is not present or is present at a lower levelin the sensor image. Merely by way of example, the aerial image caninclude a tangential image and a sagittal image that have millimeters ormore of curvature at the edge and in different directions.

It should be appreciated that the specific steps illustrated in FIG. 11provide a particular method of operating a hand-held imager to image aretina of an eye of a patient according to an embodiment of the presentinvention. Other sequences of steps may also be performed according toalternative embodiments. For example, alternative embodiments of thepresent invention may perform the steps outlined above in a differentorder. Moreover, the individual steps illustrated in FIG. 11 may includemultiple sub-steps that may be performed in various sequences asappropriate to the individual step. Furthermore, additional steps may beadded or removed depending on the particular applications. One ofordinary skill in the art would recognize many variations,modifications, and alternatives.

FIG. 12 is a simplified flowchart illustrating a method of imaging aretina of an eye of a patient according to an embodiment of the presentinvention. The method 1200 includes positioning a hand-held retinalimager adjacent the eye of the patient (1210) and obtaining a firstimage of a first portion of the retina (1212). The first image isassociated with a central area (e.g., a circular area) and a first fieldof view (e.g., 100 degrees). The first image can be formed on the imageplane of the image sensor as illustrated in FIG. 7F.

The method also includes obtaining a second image of a second portion ofthe retina (1214). The second image is associated with an annular areasurrounding the central area. The outer periphery of the annular area ischaracterized by a second field of view (e.g., 130 degrees) greater thanthe first field of view. In some embodiments, the first portion of theretina and the second portion of the retina are contiguous. The methodfurther includes combining the first image of the first portion of theretina and the second image of the second portion of the retina toprovide a combined image of the retina (1216). Utilizing embodiments ofthe present invention, the combined image provides higher quality thanavailable if a single image was obtained.

In some embodiments, the hand-held imager includes an illuminationsource operable to generate illumination light and an objective lens setincluding an objective lens and a second lens. In an embodiment,obtaining the first image of the first portion of the retina includesbringing the objective lens in contact with a cornea of the eye,illuminating the first portion of the retina with illumination lightpassing through the objective lens set, and reflecting at least aportion of the illumination light off of the first portion of the retinato provide a return signal. In some embodiments, the peripheral portionof the retina surrounding the central portion is masked off such that itis not illuminated while the first image is obtained. Obtaining thefirst image can further include directing the return signal along anoptical path and detecting a sensor image at the image plane using animage sensor.

In another embodiment, obtaining the second image of the second portionof the retina includes bringing the objective lens in contact with acornea of the eye, illuminating the second portion of the retina withillumination light passing through the objective lens set, andreflecting at least a portion of the illumination light off of thesecond portion of the retina to provide a return signal. In someembodiments, the central portion of the retina inside the peripheralportion is masked off such that it is not illuminated while the secondimage is obtained. Obtaining the second image can further includedirecting the return signal along an optical path and detecting a sensorimage at the image plane using an image sensor.

As described herein, obtaining the first image of the first portion ofthe retina can include operating a spatial light modulator to illuminatethe central area and block light propagating in the annular areasurrounding the central area. Obtaining the second image of the secondportion of the retina can include operating the spatial light modulatorto illuminate the annular area surrounding the central area and blocklight propagating in the central area. The spatial light modulator canbe located adjacent an image plane of an image sensor.

It should be appreciated that the specific steps illustrated in FIG. 12provide a particular method of imaging a retina of an eye of a patientaccording to an embodiment of the present invention. Other sequences ofsteps may also be performed according to alternative embodiments. Forexample, alternative embodiments of the present invention may performthe steps outlined above in a different order. Moreover, the individualsteps illustrated in FIG. 12 may include multiple sub-steps that may beperformed in various sequences as appropriate to the individual step.Furthermore, additional steps may be added or removed depending on theparticular applications. One of ordinary skill in the art wouldrecognize many variations, modifications, and alternatives.

FIG. 13 is a simplified flowchart illustrating a method of forming awide field of view image of a retina of an eye of a patient according toan embodiment of the present invention. The method 1300 includespositioning a hand-held retinal imager adjacent the eye of the patient(1310) and obtaining a first image of a first portion (e.g., a centralportion) of the retina. The hand-held imager can include an illuminationsource operable to generate illumination light and an objective lens setincluding an objective lens and a second lens. The first image isassociated with a central area (e.g., a circular area) and a first fieldof view (e.g., 100 degrees).

In an embodiment, obtaining the first image of the first portion of theretina includes bringing the objective lens in contact with a cornea ofthe eye and illuminating the first portion of the retina of the eye withthe illumination light passing through the objective lens set. Obtainingthe first image can also include reflecting at least a portion of theillumination light off of the first portion of the retina to provide areturn signal, directing the return signal along an optical path, anddetecting a central sensor image at the image plane using an imagesensor.

The method also includes obtaining a first additional image of a firstadditional portion of the retina (1314). The first additional imageassociated with a first azimuthal range covering a first portion of anannular area surrounding the central area. An outer periphery of theannular area is characterized by a second field of view (e.g., 150degrees) greater than the first field of view. The method furtherincludes obtaining a second additional image of a second additionalportion of the retina (1316). The second additional image is associatedwith a second azimuthal range covering a second portion of the annulararea surrounding the central area. Additionally, The method includesobtaining a third additional image of a third additional portion of theretina (1318). The third additional image is associated with a thirdazimuthal range covering a third portion of the annular area surroundingthe central area. In some embodiments, together, the first azimuthalrange, the second azimuthal range, and the third azimuthal range cover a360 degree range.

In an embodiment, obtaining the first, second, and third additionalimages of the first, second, and third additional portions of the retinaincludes bringing the obj ective lens in contact with a cornea of theeye and sequentially illuminating the first, second, and thirdadditional portions of the retina of the eye with the illumination lightpassing through the objective lens set. Obtaining the first, second, andthird additional images can also include reflecting at least a portionof the illumination light off of the first, second, and third additionalportions of the retina to provide first, second, and third returnsignals, directing the first, second, and third return signals along anoptical path, and detecting first, second, and third peripheral sensorimages at the image plane using an image sensor.

As an example, obtaining the first image of the first portion of theretina can include operating a spatial light modulator to illuminate thecentral area and block light propagating in the annular area surroundingthe central area. The spatial light modulator can be located adjacentthe image plane of the image sensor. Obtaining the first additionalimage of the first additional portion of the retina can includeoperating the spatial light modulator to illuminate the first azimuthalrange covering the first portion of the annular area surrounding thecentral area and block light propagating in the central area, in thesecond azimuthal range covering the second portion of the annular areasurrounding the central area, and in the third azimuthal range coveringthe third portion of the annular area surrounding the central area.

Obtaining the second additional image of the second additional portionof the retina can include operating the spatial light modulator toilluminate the second azimuthal range covering the second portion of theannular area surrounding the central area and block light propagating inthe central area, in the first azimuthal range covering the firstportion of the annular area surrounding the central area, and in thethird azimuthal range covering the third portion of the annular areasurrounding the central area. Obtaining the third additional image ofthe third additional portion of the retina can include operating thespatial light modulator to illuminate the third azimuthal range coveringthe third portion of the annular area surrounding the central area andblock light propagating in the central area, in the first azimuthalrange covering the first portion of the annular area surrounding thecentral area, and in the second azimuthal range covering the secondportion of the annular area surrounding the central area.

The method also includes combining the first image of the first portionof the retina, the first additional image of the first additionalportion of the retina, the second additional image of the secondadditional portion of the retina, and the third additional image of thethird additional portion of the retina to provide a combined image ofthe retina (1320).

As illustrated in FIG. 8C, the first portion of the retina can becontiguous with the first portion of the annular area surrounding thecentral area, the second portion of the annular area surrounding thecentral area, and the third portion of the annular area surrounding thecentral area. Additionally, the first portion of the annular areasurrounding the central area can be contiguous with the second portionof the annular area surrounding the central area, the second portion ofthe annular area surrounding the central area can be contiguous with thethird portion of the annular area surrounding the central area, and thethird portion of the annular area surrounding the central area can becontiguous with the first portion of the annular area surrounding thecentral area.

It should be appreciated that the specific steps illustrated in FIG. 13provide a particular method of forming a wide field of view image of aretina of an eye of a patient according to an embodiment of the presentinvention. Other sequences of steps may also be performed according toalternative embodiments. For example, alternative embodiments of thepresent invention may perform the steps outlined above in a differentorder. Moreover, the individual steps illustrated in FIG. 13 may includemultiple sub-steps that may be performed in various sequences asappropriate to the individual step. Furthermore, additional steps may beadded or removed depending on the particular applications. One ofordinary skill in the art would recognize many variations,modifications, and alternatives.

It is also understood that the examples and embodiments described hereinare for illustrative purposes only and that various modifications orchanges in light thereof will be suggested to persons skilled in the artand are to be included within the spirit and purview of this applicationand scope of the appended claims.

1. A hand held retinal imager including image guided optical coherencetomography (OCT), the hand held retinal imager comprising: anillumination source operable to generate illumination light; a beamsplitter operable to receive the illumination light and direct theillumination light along an optical axis; a field lens disposed alongthe optical axis; an objective lens disposed along the optical axis andoperable to contact a cornea of an eye, wherein the objective lens isoperable to inject the illumination light into the eye as anillumination ring; an entrance pupil, wherein the entrance pupil and theillumination ring are located at different positions along the opticalaxis; an image sensor; an imaging lens group disposed along the opticalaxis between the beam splitter and the image sensor, wherein the imaginglens group is operable to form a sensor image at the image sensor; asecond beam splitter positioned within the imaging lens group; and anOCT beam train optically coupled to the second beam splitter.
 2. Thehand held retinal imager of claim 1 further comprising a housing havinga grip operable to be held by a hand of a user.
 3. The hand held retinalimager of claim 1 wherein an aerial image is formed adjacent to thefield lens.
 4. The hand held retinal imager of claim 3 wherein theaerial image comprises an object for the sensor image at the imagesensor.
 5. The hand held retinal imager of claim 3 wherein the aerialimage is formed between the field lens and the beam splitter.
 6. Thehand held retinal imager of claim 3 wherein the objective lens isfurther operable to receive reflected light from a retina and the aerialimage is formed by the reflected light.
 7. The hand held retinal imagerof claim 1 wherein the objective lens comprises a single elementobjective lens.
 8. The hand held retinal imager of claim 7 wherein theillumination light is injected into the eye through the single elementobjective lens.
 9. The hand held retinal imager of claim 1 wherein theOCT beam train comprises a micro-electromechanical system (MEMS) mirror.10. The hand held retinal imager of claim 9 where a pupil is formed onthe MEMS mirror.
 11. The hand held retinal imager of claim 1 wherein asingle fiber is utilized to transmit and receive light propagating alongthe OCT beam train.
 12. The hand held retinal imager of claim 1 whereinthe sensor image comprises a central area.
 13. The hand held retinalimager of claim 12 wherein the central area is circular.
 14. The handheld retinal imager of claim 12 wherein the sensor image furthercomprises an annular area surrounding the central area.
 15. The handheld retinal imager of claim 14 wherein a periphery of the central areaforms a common border with an inner periphery of the annular area. 16.The hand held retinal imager of claim 12 wherein the sensor imagefurther comprises three azimuthal segments.
 17. The hand held retinalimager of claim 16 wherein the central area is defined by a first fieldof view of a first width and each of the three azimuthal segments isdefined by a second field of view extending from the first width to asecond width.
 18. The hand held retinal imager of claim 17 wherein thefirst width is 15° and the second width is 22.5°.